Sleep disturbance affects millions of Americans and costs billions of dollars each year. The cumulative long-term effects of sleep disturbance have been associated with a wide range of deleterious health consequences including systemic inflammation, immune dysfunction, and neuroendocrine abnormalities, resulting in increased risks for obesity, hypertension, diabetes, and cardiovascular diseases. Geographic difference in the prevalence of sleep disturbance has been documented for several decades, but the contributing environmental factors remain largely unknown. Animal experiments have demonstrated disorganization of sleep induced by exposure to ozone, through alterations of sleep-related neurotransmitters. Recent research in air pollution toxicity has shown that particulate matter (PM) exposures can induce both neurotoxic and adverse systemic reactions including oxidative stress and inflammatory responses. Although these toxicological data support the role of ambient air pollutants in sleep disturbance, no epidemiologic investigation has been conducted for this pathophysiologically plausible effect. The proposed cohort study targets an important population subgroup identified by the NIH and aims to investigate ambient air pollutants as novel determinants of sleep disturbance in postmenopausal women. We draw on the completed Women's Health Initiative Clinical Trials (WHI-CT) and two NIH-supported studies to address these important questions in an efficient manner. We will examine the association between exposure to ambient air pollution and sleep disturbance and assess how the hypothesized effects of ambient air pollutants contribute to the spatial variability of sleep disturbance in a geographically-diverse cohort of women aged 50-79 at study inception. The proposed study takes advantage of the extant high-quality longitudinal data on sleep disturbance and biophysical attributes of the well- characterized WHI-CT cohort. Further, we are able to incorporate the air pollution data for all WHI-CT participants assembled by an NIEHS-funded ancillary study and have validated its exposure estimation methodology based on the criteria pollutants data recorded in the EPA Air Quality System. For this application, longitudinal sleep profiles of 68,133 women, including the validated WHI-Insomnia Rating Scale, will be examined in multi-level analyses for their associations with residence-level exposure to ambient air pollutants, with primary focus on PM and ozone. Potential modifications of these putative associations by individual's biophysical attributes will be analyzed to identify subpopulations more susceptible to sleep disturbance related to adverse ambient environment. This innovative epidemiologic investigation of neurobehavioral effects of exposure to ambient air pollution will extend our knowledge in a novel area of research on environmental determinants of sleep disorders. Environmental Determinants of Sleep Disturbance: Role of Ambient Air Pollution Project Narrative Sleep disturbance affects millions of Americans and increases risks for obesity, hypertension, diabetes, and cardiovascular diseases. Animal experiments have demonstrated disorganization of sleep induced by exposure to air pollution, but no studies have examined the role of ambient air pollution as a determinant of sleep disturbance in humans. Expected results from this proposed first epidemiologic study on the effect of ambient air pollution on sleep disturbance will have major implications for public health policies and clinical care for patients with sleep disorders. [unreadable] [unreadable] [unreadable] [unreadable]